: The Laboratory of Neuro Imaging Resource (LONIR) will create and apply innovative solutions for the investigation of imaging, genetics, behavioral and clinical data. The methods that we produce enable population-based analysis in numerous healthy and disease cohorts. We build upon our considerable prior progress in this competitive renewal proposal to focus our LONIR Technology Research and Development (TR&D) projects on three specific areas. TR&D 1 (Image Understanding) focuses on methodological developments for the analysis of brain imagery including robust image segmentation and registration, quality assurance and evaluation of image processing results, and processing of structural and diffusion brain data. TR&D 2 (Connectomics) will advance the study of brain connectivity using diffusion imaging and its powerful extensions. This project will go beyond tensor models of diffusion for assessing fiber integrity and connectivity, develop tract-based statistical analysis tools, introduce novel connectivity mapping approaches, and provide mechanisms for studying the genetics of brain connectivity. TR&D 3 (Data Interpretation) will utilize the imaging feature information extracted using tools from TR&D 1 and 2 and enable the interpretation of the resulting data, to address relevant biologically questions by providing tools for the selection of appropriate statistical models and the visual examination and interpretation of results. These research activities are tightly coupled and address the needs and requirements that have been presented to us by our Driving Biological Projects and Service Collaborators. These projects form a well-integrated program for the characterization, measurement, modeling, analysis, interpretation, and understanding of multifaceted patterns of structural and functional brain data. LONIR will facilitate studies of dynamically changing anatomical frameworks, e.g., developmental, neurodegenerative, traumatic, metastatic, by providing tools for comprehensive understanding of the nature and extent of these processes. These research efforts are supported by integrated Infrastructure, Dissemination, Training and Dissemination cores.